Eosinophilic esophagitis is an allergic inflammatory disease characterized by elevated eosinophils in the esophagus. This inflammatory condition of the esophagus affects both children and adults, and men more than women.
Eosinophilic esophagitis is a newly recognized disease that over the past decade has been increasingly diagnosed. It is a rare disease, but increasing in prevalence to an estimated 1:2000. This increase is thought to reflect an increase in diagnosis, as well as a true increase in eosinophilic esophagitis cases. Fortunately, the medical community is responding and new scientific information is emerging to guide management of this disorder, which often persists with ongoing or recurrent symptoms.
The major symptom in adults with eosinophilic esophagitis is dysphagia (problems of swallowing) for solid food. Eosinophilic esophagitis stiffens the esophagus so that solid foods have difficulty passing through the esophagus into the stomach. Other common causes of dysphagia for solid food are esophageal strictures and Schatzki rings. The diagnosis of eosinophilic esophagitis usually is made during an endoscopy (EGD), performed for the evaluation of dysphagia and is confirmed by biopsy of the esophagus.
People with eosinophilic esophagitis commonly have other allergic diseases such as rhinitis, asthma, and/or eczema. Eosinophilic esophagitis can be driven by food allergy or intolerance: most patients who eliminate food proteins from their diet (by drinking only an amino-acid based formula) improve. The disease may also be triggered by other environmental factors that researchers are beginning to understand.
There are a number of studies that have demonstrated the central role of food allergens in triggering eosinophilic esophagitis. When these allergenic foods are removed from a person's diet, symptoms can resolve and the eosinophilic inflammation in the esophagus can be healed.
In addition, there are medical therapies available—the most common drug therapy is the use of swallowed inhaled steroids such as budesonide (Pulmicort) made into a slurry or fluticasone (Flovent) inhalers. Presently these therapies are off-label treatments as there no approved drug medications with this clinical indication.
The selected steroid of this invention is fluticasone propionate, a compound with potent anti-inflammatory activity widely used for the treatment of respiratory diseases.
Fluticasone propionate is an old drug described firstly in British Patent 2088877. There are several different dosage forms commercially available, such as oral tablets, inhalation dry powders, oral inhalation aerosol, nasal sprays, topical dermatological cream and ointments etc.
Novel fluticasone formulations with at least one surface stabilizer and particle size of less than about 2000 nm are described in WO2004/069225. The formulations described in this patent are mainly for treating respiratory related illness. There is no mention of gastrointestinal diseases in general nor, specifically, of eosinophilic esophagitis.
Orally administered corticosteroid compositions are described in WO2011/041509. This application is primarily directed to solid dispersible dosage forms also in presence of bioadhesive polymers. There are described moreover liquid bioadhesive formulations, mainly non aqueous. There is no mention of viscous sugar free aqueous liquid formulations of fluticasone propionate.
None of the known prior art describes a viscous sugar free liquid formulation of fluticasone propionate specifically designed for treatment of eosinophilic esophagitis.
There is therefor a need in the art for orally administered steroid formulations specifically designed for the treatment of eosinophilic esophagitis that can decrease frequency of administration, improve clinical efficacy and reduce side effects associated with the use of steroids.